What is the normal function of the YWHAE gene?

The YWHAE gene provides instructions for making the 14-3-3 epsilon (ε) protein, which is part of the large 14-3-3 protein family. Proteins in this family attach (bind) to other proteins involved in cell signaling. 14-3-3 proteins either turn on (activate) or turn off (inactivate) these other proteins. The 14-3-3ε protein helps to regulate a variety of processes including cell division and sensitivity to insulin, a hormone that helps control blood sugar levels.

The 14-3-3ε protein is active in tissues throughout the body, although its function is sometimes unclear. In the brain, this protein is involved in directing the movement of nerve cells (neuronal migration) by binding to other proteins involved in this process. It is thought that the 14-3-3ε protein is critical for proper neuronal migration and normal brain development.

How are changes in the YWHAE gene related to health conditions?

The characteristic signs and symptoms of Miller-Dieker syndrome are caused by a deletion of genetic material near the end of the short (p) arm of chromosome 17. The chromosomal region that is typically deleted contains multiple genes, including the YWHAE gene. As a result of the deletion, people with this condition have only one copy of the YWHAE gene in each cell instead of the usual two copies.

A deletion of one copy of the YWHAE gene in each cell reduces the amount of 14-3-3ε protein by about half. A shortage of 14-3-3ε protein increases the severity of lissencephaly (a problem with brain development in which the surface of the brain is abnormally smooth) in people with Miller-Dieker syndrome.

other disorders - caused by mutations in the YWHAE gene

A deletion that only involves the YWHAE gene can also cause health problems. People with a YWHAE gene deletion are missing one copy of the gene in each cell, which reduces the amount of 14-3-3ε protein that is produced by about half. A deficiency (shortage) of this protein is thought to cause short stature; intellectual disability; and distinctive facial features including a prominent forehead, wide nasal bridge, and small jaw. People with a YWHAE gene deletion do not have lissencephaly but tend to have other brain abnormalities.

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